Acute hepatitis as a manifestation of primary HSV infection in a healthy child

Several herpesviruses can cause hepatic injury, but herpes simplex virus (HSV) is rarely involved in immune-competent patients, beyond the neonatal age. We report a rare case of acute hepatitis associated with primary HSV infection in a previously healthy child. Therefore, HSV infection should be actively investigated in healthy children developing acute hepatitis without acute liver failure, if the most common infectious agents have been excluded, despite the absence of the typical vesicular herpetic skin and/or mucosal manifestations

Metabolic alkalosis with multiple salt unbalance: an atypical onset of cystic fibrosis in a child

Dehydration with multiple salt abnormalities is frequently encountered in the paediatric emergency department, during acute illnesses complicated by loss of body fluids. Metabolic alkalosis is not a common finding in dehydrated children. The presence of unusual electrolyte unbalance, such as metabolic alkalosis, hyponatremia, hypochloremia and hypokalemia, without evidence of renal tubular defects, is named as pseudo-Bartter syndrome. It can occur in several clinical settings and, in infancy, it is described as a potential complication of cystic fibrosis. We report a case of pseudo-Bartter syndrome representing the onset of cystic fibrosis in childhood

Increased total serum immunoglobulin E in children developing mycoplasma pneumoniae-related extra-pulmonary diseases

Mycoplasma pneumoniae has been recognized to be involved in several extra-pulmonary diseases, but the underlying immunologic mechanisms are still largely unknown. Recently, we observed a significant elevation of serum Immunoglobulin E (IgE) in a small group of these children. Here, we assessed total serum IgE levels in children affected with Mycoplasma pneumoniae-related extra-pulmonary diseases. We prospectively collected the data of 162 children admitted to the hospital (because of respiratory infections or extra-pulmonary diseases) who were evaluated for Mycoplasma pneumoniae serology and total serum IgE levels, concomitantly. Based upon clinical and serology aspects, 3 groups of children were identified: I) with non-mycoplasma respiratory disease; II) with mycoplasma-related respiratory diseases; III) with extra-pulmonary diseases related to concomitant/recent Mycoplasma pneumoniae infection. Interestingly, children with Mycoplasma pneumoniae-related extra-pulmonary diseases showed a significant elevation of total serum IgE. In particular, patients developing Mycoplasma pneumoniae-related extra-pulmonary diseases (group III) showed significantly higher level of IgE than both previous groups (p<0.001 vs. group I; p<0.01 vs. group II). In conclusion, hospitalized children diagnosed with Mycoplasma pneumoniae-related extrapulmonary diseases resulted to have significantly increased serum IgE compared to children developing respiratory illnesses only

Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3

Objective: To retrospectively investigate safety and efficacy of nusinersen in a large cohort of adult Italian patients with spinal muscular atrophy (SMA). Methods: Inclusion criteria were: (1) clinical and molecular diagnosis of SMA2 or SMA3; (2) nusinersen treatment started in adult age (>18 years); (3) clinical data available at least at baseline (T0-beginning of treatment) and 6 months (T6). Results: We included 116 patients (13 SMA2 and 103 SMA3) with median age at first administration of 34 years (range 18-72). The Hammersmith Functional Rating Scale Expanded (HFMSE) in patients with SMA3 increased significantly from baseline to T6 (median change +1 point, p<0.0001), T10 (+2, p<0.0001) and T14 (+3, p<0.0001). HFMSE changes were independently significant in SMA3 sitter and walker subgroups. The Revised Upper Limb Module (RULM) in SMA3 significantly improved between T0 and T14 (median +0.5, p=0.012), with most of the benefit observed in sitters (+2, p=0.018). Conversely, patients with SMA2 had no significant changes of median HFMSE and RULM between T0 and the following time points, although a trend for improvement of RULM was observed in those with some residual baseline function. The rate of patients showing clinically meaningful improvements (as defined during clinical trials) increased from 53% to 69% from T6 to T14. Conclusions: Our data provide further evidence of nusinersen safety and efficacy in adult SMA2 and SMA3, with the latter appearing to be cumulative over time. In patients with extremely advanced disease, effects on residual motor function are less clear

Ofatumumab versus Teriflunomide in Multiple Sclerosis

BACKGROUND: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known. METHODS: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume. RESULTS: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups. CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. (Funded by Novartis; ASCLEPIOS I and II ClinicalTrials.gov numbers, NCT02792218 and NCT02792231.)